SBIR Phase I proposal to NIH requests $183,000 funding for Chromatan, Inc. to demonstrate the feasibility of using Continuous Countercurrent Tangential Chromatography (CCTC) for the purification of high value biological products, e.g., monoclonal antibodies for the treatment of cancer or recombinant vaccines for protection against viral disease or a flu pandemic. Downstream processing currently accounts for as much as 80% of the overall cost of production of recombinant protein products. Recent advances in cell culture technology have created a "downstream bottleneck" due to the limited capacity and high expense of packed bed chromatography columns. CCTC overcomes many of the limitations of conventional column chromatography by using resin particles in the form of a slurry, which is pumped through a disposable flow path consisting of a series of static mixers and hollow fiber membrane modules. Countercurrent recycling of the permeate is used to significantly increase process efficiency and reduce resin and buffer requirements, analogous to the behavior in countercurrent liquid-liquid extraction. The optimal membrane pore size, resin particle size, and operating conditions for CCTC (e.g. crossflow rate, permeate flow rate, and residence time in the static mixers) will be determined from experimental measurements of the critical filtrate flux and the binding / elution kinetics. CCTC can employ much smaller resin particles than packed bed columns, since there is no longer any pressure drop limitation, which can provide significantly faster mass transfer rates. The overall goal of the proposed research is to design, construct, and test a prototype CCTC system capable of separating a model protein mixture with greater than 90% product yield and 95% purity. Chromatan envisions that CCTC technology will provide the following favorable impacts for large-scale commercial applications of chromatography: 5-fold reduction in resin volume requirements compared with column chromatography;a disposable flow path that eliminates the need for costly cleaning validation;straightforward scalability up to batch volumes of 20,000 L;significant reduction of capital costs (up to 60%) in large-scale operations;significant overall cost savings (up to 75%) for capture chromatography steps. The continuous and disposable nature of this technology will improve public health by decreasing time to market and reducing production costs, both of which will lead to a reduction in drug costs. Chromatan projects a fifth year market peneratraion of 10% and revenues of $100 million. PUBLIC HEALTH RELEVANCE: The overall goal of the proposed SBIR project is to design, construct, and test a Continuous Countercurrent Tangential Chromatography system capable of providing highly efficient and low cost purification of therapeutic proteins and vaccines. CCTC is designed to have a disposable flow path, continuous operation, and lower capital and operating costs compared to current separation technologies, and will lead to significant improvements in public health by reducing the cost of important drug products, and by decreasing the time required to bring new therapeutic drugs to market.